PREPARE BY: Miss lock shu ping

1. CHAPTER 7.0: MUTATION PREPARE BY: Miss lock shu ping

3. Explain mutation Classify mutation into ‘gene mutation’ and ‘chromosomal mutation’. State the types of mutation Define mutagen State types of mutagen

4. MUTATION ?

5. A permanent change in the amount, arrangement or structure of the DNA of an organism which can passed down to the next generation.

6. WHAT IS MUTATION? ‘Changes in the genetic material (genes or chromosomes) of a cell’ Can be inherited if mutation occurs in reproductive cells during formation of gametes

7. Types of mutation Based on the cause Spontaneous mutation Induced mutation • - mistakes happen spontaneously during DNA replication, DNA repair, or DNA recombination. • e.g: nondisjunction during meiosis • ( details will be explain in 16.3) • mutations that cause by mutagen -e.g: exposure to mutagen

8. Spontaneous Mutation mistakes happen spontaneously during DNA replication, DNA repair, or DNA recombination.

9. Induced Mutation • Mutations that cause by mutagen A variety of agents increase the frequency of mutation

10. Mutation agent (Mutagen) • Physical and chemical agents that induces changes in DNA • Physical agent: • Ultraviolet ray • Ionizing radiation (X-ray, gamma ray, alpha particles, neutron and electron) • Chemical agent: • Mustard gas, nitrous acid, base analogue etc. • Colchicine , ethidium bromide

11. Physical agent

12. Chemical agent

13. Shortwave UV (UVA) Causes ThymidineDimers

14. Mutation that causes by agent orange . About 500 000 children in Vietnam born with birth defects during Vietnam war

15. Mutant • A mutated gene, alternatively, • An organism carrying a gene that has undergone a mutation that • shows new phenotype traits as a result from mutation

16. New phenotypes traits showed by this children as a result of mutation

17. Mutation classification By effect on structure of gene (involve small scale mutation) of chromosome (involve large scale mutation) Genetic Mutation • Base substitution • Base insertions • Base deletions • Base inversion • Chromosomal Mutation • Structural change / Chromosome Aberration • Alterations of chromosome number • Aneuploidy • Euploidy / Polyploidy

18. Mutation Genetic Mutation Chromosomal Mutation Base substitution Base insertions Base deletions Base inversion

19. Explain gene mutation Classified gene mutation Describe base substitution as point mutation Explain frameshift mutation Descibebase insertion as a frameshift mutation Describe base deletion as a frameshift mutation

20. 16.2 Gene Mutation/ Point Mutation • A type of mutation which involved • A change in the nucleotide sequence of the DNA within a gene change the amino acid sequence and thus, changes the protein Different protein produced as the effect of mutation may not function as normal Example : sickle cell anemia

21. Change the DNA nucleotide sequence change the amino acid sequence changes the protein

22. AGCTTA AGCGTA AGCTA AGTCTA TCGAAT TCGCAT TCGAT TCAGAT AGCGTTA TCGCAAT Gene Mutation Normal Insertion Substitution Deletion Inversion

23. Classification of gene mutation • Base substitution – one or a few base pairs in the nucleotide sequences in genes is substitute (replaced) • Base insertions – addition of 1 or a few base pairs in the nucleotide sequences in genes • Base deletions – loss of 1 or a few base pairs in nucleotide sequences • Base inversion – 2 base pairs or more are inverted in nucleotide sequence

24. AGCTA AGCTTA AGTCTA AGCGTA TCGAAT TCAGAT TCGAT TCGCAT AGCGTTA TCGCAAT Analogy that can be made to show point mutation • Base Substitution : • THE FAT CAT ATE THE RAT • THE FAT CAR ATE THE RAT Normal Deletion Substitution Insertion Inversion • THE FAT CAT ATE THE RAT • THE FAT CAT CAT ETH ERA • Base Insertion: • Base Deletion : • THEFATCAT ATE THE RAT • THE ATC ATA TET HER AT • Base Inversion : • THE FAT CAT ATE THE RAT • THE FAT CAT ATE THE TAR

25. one or a few base pairs in the nucleotide sequences in genes is replaced with another base pairs. • Can cause changes in base sequence – results in changes of codon . E.g: (UAU change to UGU) • 1 codon = 3 base/ nucleic acid (coding for 1 amino acid)

26. only on a • small point of a chromosome Before mutation CAC-AAG-UAU-CAC-UAA his lystyr his stop CAC-AAG-UGU-CAC-UAA his lyscys his stop Substitution mutation Point Mutation a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA.

27. Changes in codon: Missense mutation nonsense mutation • Leads to amino acid changes • The altered codon codes for • different amino acid • Changes a codon to stop • codon(UAG / UAA / UGA ) • Leading to a nonfunctional • protein

28. Changes in codon Nonsense Mutation • changes a codon to stop codon • Leading to a nonfunctional protein

29. Changes in codon Missense Mutations • Leads to amino acid changes • the altered codon codes for an amino acid that is not the right sense.

30. Changes in codon Silent Mutations • have no effect on the encoded protein. • a change in a base pair transform one codon into another that translated into the same amino acid. • happens because of redundancy in the genetic code.

31. Silent Mutations AGU AGC SER  SER

32. Changes in codon: Missense mutation nonsense mutation • Leads to amino acid changes • The altered codon codes for • different amino acid • Changes a codon to stop • codon(UAG / UAA / UGA ) • Leading to a nonfunctional • protein

33. Base substitution Before mutation CAC-AAG-UAU-CAC-UAA his lystyr his stop CAC-AAG-UGU-CAC-UAA his lyscys his stop CAC-AAG-UAG his lysstop Missense mutation Nonsense mutation Differences between missense and nonsense mutation is missense mutation altered codon codes for different amino acid while nonsense mutation alterescodon to stop codon.

34. Sickle cell Anemia Effect of Base substitution

35. SICKLE-CELL ANEMIA Encode by different gene Missense mutation Abnormal Hb – Sickle (S) shape Defective red blood cell Hb ~ 4 polypeptide chain (2- & 2-)

36. HOW SICKLE-CELL ANEMIA HAPPEN? Happens because substitution mutation Amino acid valine replaces glutamic acidat a single position in the protein (-strand) Patient suffer from anemia ~ Hb-S stiff & tend to accumulate in small capillary Hb is not efficient of transporting oxygen

37. Missense mutation

38. Sickle cell Anemia • abnormal haemoglobin crystallizes & erythrocyte is pulled into a sickle shape • the cells fragment easily or clump together to clog the capillaries (and less O2 is transported)

39. TRY THIS… State what type of gene mutation below: Normal DNA : GGCCTT GGCATT GGCCATT GGCTT GCGCTT GGCATT BASE SUBSTITUTION GGCCATT BASE INSERTION GGCTT BASE DELETION GCGCTT BASE INVERSION

40. WHAT ARE THE DIFFERENCES BETWEEN MISSENSE AND NONSENSE MUTATIO N? nonsense mutation Missense mutation altered codon codes for differentamino acid altered codon to STOPcodon. (UAG / UAA / UGA )

41. What is the genetic disorder shown above? Sickle- cell anemia What type of gene mutation that cause this genetic disorder to happen? Why? Because of substitution mutation. Amino acid valine is replaced by glutamic acidat a single position in the protein (-strand)

44. Point Mutations in Coding Sequences Missense – changes amino acid Nonsense – creates stop codon Frameshift – alters remainder of reading frame results in completely different amino acid sequence.

47. Frame-shift Mutations

48. Involveinsertion/deletion of a base pair or more into the nucleotides sequence of DNA • Many of these deletions/insertion start in the middle of a codon

49. Shifting the reading frame by one or two bases • Frame shift mutations cause the gene to be read in theWRONGthree base groups (codon)

50. Example Insertion of U base Change the sequence of amino acids Deletion of C base Resulting in stop codon-no further amino acid produces